Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?

Yvette C. Wong, Kelvin Luk, Kerry Purtell, Samuel Burke Nanni, A. Jon Stoessl, Louis Eric Trudeau, Zhenyu Yue, Dimitri Krainc, Wolfgang Oertel, Jose A. Obeso*, Laura A. Volpicelli-Daley

*Corresponding author for this work

Research output: Contribution to journalReview article

4 Scopus citations

Abstract

While current effective therapies are available for the symptomatic control of PD, treatments to halt the progressive neurodegeneration still do not exist. Loss of dopamine neurons in the SNc and dopamine terminals in the striatum drive the motor features of PD. Multiple lines of research point to several pathways which may contribute to dopaminergic neurodegeneration. These pathways include extensive axonal arborization, mitochondrial dysfunction, dopamine's biochemical properties, abnormal protein accumulation of α-synuclein, defective autophagy and lysosomal degradation, and synaptic impairment. Thus, understanding the essential features and mechanisms of dopaminergic neuronal vulnerability is a major scientific challenge and highlights an outstanding need for fostering effective therapies against neurodegeneration in PD. This article, which arose from the Movement Disorders 2018 Conference, discusses and reviews the possible mechanisms underlying neuronal vulnerability and potential therapeutic approaches in PD.

Original languageEnglish (US)
Pages (from-to)1406-1422
Number of pages17
JournalMovement Disorders
Volume34
Issue number10
DOIs
StatePublished - Oct 1 2019

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Keywords

  • Parkinson
  • dopamine
  • substantia nigra
  • synaptic
  • synuclein

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Wong, Y. C., Luk, K., Purtell, K., Burke Nanni, S., Stoessl, A. J., Trudeau, L. E., Yue, Z., Krainc, D., Oertel, W., Obeso, J. A., & Volpicelli-Daley, L. A. (2019). Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals? Movement Disorders, 34(10), 1406-1422. https://doi.org/10.1002/mds.27823